Importance of social vulnerability on long-term outcomes after heart transplantation.

The relationship between social determinants of health and outcomes after heart transplantation has not been examined. The social vulnerability index (SVI) uses United States census data to determine the social vulnerability of every census tract based on 15 factors. This retrospective study seeks to examine the impact of SVI on outcomes after heart transplantation. Adult heart recipients who received a graft between 2012 and 2021 were stratified into SVI percentiles of <75% and SVI of ≥75%. The primary endpoint was survival. The median SVI was 48% (interquartile range: 30%-67%) among 23 700 recipients. One-year survival was similar between groups (91.4 vs 90.7%, log-rank P = .169); however, 5-year survival was lower among individuals living in vulnerable communities (74.8% vs 80.0%, P < .001). This finding persisted despite risk adjustment for other factors associated with mortality (survival time ratio 0.819, 95% confidence interval: 0.755-0.890, P < .001). The incidences of 5-year hospital readmission (81.4% vs 75.4%, P < .001) and graft rejection (40.3% vs 35.7%, P = .004) were higher among individuals living in vulnerable communities. Individuals living in vulnerable communities may be at increased risk of mortality after heart transplantation. These findings suggest there is an opportunity to focus on these recipients undergoing heart transplantation to improve survival.

Optimizing Nicorandil for Spinal Cord Protection in a Murine Model of Complex Aortic Intervention.

There are currently no clinically utilized pharmacological agents for the induction of metabolic tolerance to spinal cord ischemia-reperfusion injury in the setting of complex aortic intervention. Nicorandil, a nitric oxide donor and ATP-sensitive potassium (KATP) channel opener, has shown promise in neuroprotection. However, the optimized clinical application of the drug and its mechanism of neuroprotection remains unclear. We hypothesized that 3-days pretreatment would confer the most effective neuroprotection, mediated by mitochondrial KATP channel activation. Spinal cord injury was induced by 7 minutes of thoracic aortic cross-clamping in adult male C57BL/6 mice. Time course: mice received 0.1 mg/kg nicorandil for 10 min, 4 hours, and 3 consecutive days prior to ischemia compared with control. Dose challenge: mice received 3-days nicorandil pretreatment comparing 0.1 mg/kg, 1.0 mg/kg, 5.0 mg/kg, and saline administration. Mitochondrial KATP channel blocker 5-hydroxy-decanoate (5HD) was co-administered to elucidate mechanism. Limb motor function was evaluated, and viable anterior horn neurons quantified. Nicorandil pretreatment at 4 hours and 3 days before ischemia demonstrated significant motor function preservation; administration 10 minutes before ischemia showed no neuroprotection. All nicorandil doses showed significant motor function preservation. Three days administration of Nicorandil 1.0 mg/kg was most potent. Neuroprotection was completely abolished by 5HD co-administration. Histological analysis showed significant neuron preservation with nicorandil pretreatment, which was attenuated by 5HD co-administration. Three days administration of Nicorandil 1.0 mg/kg showed near-total motor function preservation in a murine spinal cord ischemia-reperfusion model, mediated by the mitochondrial KATP channel.

Injectable and Self-Healing Hydrogels with Double-Dynamic Bond Tunable Mechanical, Gel-Sol Transition and Drug Delivery Properties for Promoting Periodontium Regeneration in Periodontitis.

Injection of a hydrogel loaded with drugs with simultaneous anti-inflammatory and tissue regenerating properties can be an effective treatment for promoting periodontal regeneration in periodontitis. Nevertheless, the design and preparation of an injectable hydrogel with self-healing properties for tunable sustained drug release is still highly desired. In this work, polysaccharide-based hydrogels were formed by a dynamic cross-linked network of dynamic Schiff base bonds and dynamic coordination bonds. The hydrogels showed a quick gelation process, injectability, and excellent self-healing properties. In particular, the hydrogels formed by a double-dynamic network would undergo a gel-sol transition process without external stimuli. And the gel-sol transition time could be tuned by the double-dynamic network structure for in situ stimuli involving a change in its own molecular structure. Moreover, the drug delivery properties were also tunable owing to the gel-sol transition process. Sustained drug release characteristics, which were ascribed to a diffusion process, were observed during the first stage of drug release, and complete drug release owing to the gel-sol transition process was achieved. The sustained drug release time could be tuned according to the double-dynamic bonds in the hydrogel. The CCK-8 assay was used to evaluate the cytotoxicity, and the result showed no cytotoxicity, indicating that the injectable and self-healing hydrogels with double-dynamic bond tunable gel-sol transition could be safely used in controlled drug delivery for periodontal disease therapy. Finally, the promotion of periodontal regeneration in periodontitis in vivo was investigated using hydrogels loaded with ginsenoside Rg1 and amelogenin. Micro-CT and histological analyses indicated that the hydrogels were promising candidates for addressing the practical needs of a tunable drug delivery method for promoting periodontal regeneration in periodontitis.

A review of methods to measure tendon dimensions.

Tendons are soft tissues of the musculoskeletal system that are designed to facilitate joint movement. Tendons exhibit a wide range of mechanical properties matched to their functions and, as a result, have been of interest to researchers for many decades. Dimensions are an important aspect of tendon properties.Change in the dimensions of tissues is often seen as a sign of injury and degeneration, as it may suggest inflammation or general disorder of the tissue. Dimensions are also important for determining the mechanical properties and behaviours of materials, particularly the stress, strain, and elastic modulus. This makes the dimensions significant in the context of a mechanical study of degenerated tendons. Additionally, tendon dimensions are useful in planning harvesting for tendon transfer and joint reconstruction purposes.Historically, many methods have been used in an attempt to accurately measure the dimensions of soft tissue, since improper measurement can lead to large errors in the calculated properties. These methods can be categorised as destructive (by approximation), contact, and non-contact and can be considered in terms of in vivo and ex vivo.

Synergetic Induction of NGF With Diazoxide and Erythropoietin Attenuates Spinal Cord Ischemic Injury.

BACKGROUND: Paraplegia remains a significant complication of thoracoabdominal aortic intervention. We previously reported that diazoxide (DZ), enhances the neuroprotective efficacy of erythropoietin (EPO). We hypothesized that DZ and EPO combined treatment attenuates spinal cord ischemic injury through upregulation of nerve growth factor (NGF). METHODS: DZ (pretreatment) was given to adult male C57/BL6 mice by oral gavage and EPO (before surgery) was intraperitoneally injected 32 h after administration of DZ. Spinal cords were harvested 0, 2, 4, and 6 h after injection of EPO. NGF expression was analyzed by western blot. After determining the optimal time, NGF expression was compared between DZ (pretreatment) + EPO (before surgery), DZ + PBS, PBS + EPO, and PBS + PBS (ischemic control). Four groups were studied to compare the motor function after ischemia: DZ + EPO (n = 11), ischemic control (n = 9), DZ + EPO + tropomyosin receptor kinase A receptor inhibitor (n = 9), and sham (without cross-clamp, n = 4). Spinal cord ischemia was induced by a 4-min thoracic aortic cross-clamp. Functional scoring (Basso Mouse Score) was done at 12-h intervals until 48 h, and spinal cords were harvested for evaluation of NGF expression and histological changes. RESULTS: NGF expression was significantly upregulated 4 h after administration of EPO. At 4 h after injection of EPO, NGF expression in the DZ + EPO group was significantly higher than that in the other groups. DZ + EPO significantly preserved motor function compared with all other groups. At 48 h after reperfusion, the level of NGF expression in the DZ + EPO group, was significantly higher than in all other groups. CONCLUSIONS: DZ + EPO attenuates spinal cord ischemic injury through upregulation of NGF. Better understanding of this mechanism may serve to further prevent ischemic complications for aortic intervention.

Innominate Versus Axillary Artery Cannulation for the Hemiarch Repair.

BACKGROUND: Innominate artery cannulation has gained some popularity over the last decade as an alternative to axillary artery cannulation for providing selective antegrade cerebral perfusion during repair of the ascending aorta and arch. Innominate artery cannulation provides several advantages including avoidance of an additional incision and use of a larger caliber artery to provide less resistance to high flow during bypass and selective antegrade cerebral perfusion. We hypothesize that these advantages make innominate artery cannulation superior to axillary artery cannulation as it can decrease operative times and potentially decrease blood loss. METHODS: This was a single-center retrospective analysis of 206 patients who underwent hemiarch replacement between 2009 and 2017. All patients qualified including emergent cases. Groups were separated by mode of cannulation: axillary and innominate. Outcomes evaluated included cardiopulmonary bypass (CPB) time, cross-clamp time, circulatory arrest (CA) time, postoperative transfusions, intensive care unit length of stay, development of any neurological complications, end-organ failure, and mortality. Subgroup analysis was performed for elective and emergent cases. RESULTS: Axillary and innominate artery cannulation accounted for 37% (n = 77) and 67% (n = 129) of cases, respectively. There was no difference in patient characteristics except for a higher incidence of renal disease in the axillary group (16% versus 6%, P = 0.05). More emergent cases were performed in the axillary group (61% versus 17%, P < 0.001). Innominate cases had shorter CPB times (189 versus 150 min, P < 0.001) and CA (22.5 versus 11 min, P < 0.001) times overall. In the elective subgroup, CA times were shorter for the innominate cases. However, the emergent subgroup displayed no difference in operative times. Less transfusions were given in the innominate group including units of red blood cells (2 [0-6] versus 0 [0-2], P < 0.001), units of platelets (2 [1-3] versus 1 [0-2], P = 0.001), and units of plasma (6 [2-9] versus 2 [0-4], P < 0.001). A similar trend was observed in the elective subgroup. No difference in transfusions was observed in the emergent subgroup. There was no statistical difference in remaining outcomes between cases of axillary and innominate cannulation in the combined, elective, and emergent groups. CONCLUSIONS: Alternate cannulation strategies for open arch anastomoses are evolving with a trend toward using the innominate artery. These data suggest that innominate cannulation is at least equivalent to, and may be superior to, axillary cannulation. The innominate artery provides a larger conduit vessel for perfusion and this decrease in resistance to flow, allowing for faster cooling and rewarming, maybe why CPB times were lower in this group. Innominate cannulation is a safe and potentially advantageous technique for hemiarch repair.

Construction of a High-Efficiency Drug and Gene Co-Delivery System for Cancer Therapy from a pH-Sensitive Supramolecular Inclusion between Oligoethylenimine- graft-ß-cyclodextrin and Hyperbranched Polyglycerol Derivative.

Introducing genes into drug-delivery system for a combined therapy has become a promising strategy for cancer treatment. However, improving the in vivo therapy effect resulted from the high delivery efficiency, low toxicity, and good stability in the blood remains a challenge. For this purpose, the supramolecular inclusion was considered to construct a high-efficiency drug and gene co-delivery system in this work. The oligoethylenimine-conjugated ß-cyclodextrin (ß-CD-PEI600) and benzimidazole-modified four-arm-polycaprolactone-initiated hyperbranched polyglycerol (PCL-HPG-BM) were synthesized as the host and guest molecules, respectively, and then the co-delivery carrier of PCL-HPG-PEI600 was formed from the pH-mediated inclusion interaction between ß-CD and BM. PCL-HPG-PEI600 showed the improved drug (doxorubicin, DOX) and gene (MMP-9 shRNA plasmid, pMMP-9) delivery ability in vivo, and their cellular uptake and intracellular delivery were investigated. Particularly, PCL-HPG-PEI600 showed excellent pMMP-9 delivery ability with significantly higher transfection efficiency than PEI25k due to its excellent serum resistance. For the combined therapy to breast cancer MCF-7 tumor, the co-delivery system of PCL-HPG-PEI600/DOX/pMMP-9 resulted in a much better inhibition effect on MCF-7 cell proliferation and migration in vitro as well as the suppression effect on MCF-7 tumors in vivo compared to those of single DOX or pMMP-9 formulation used. Moreover, PCL-HPG-PEI600 displayed nontoxicity and excellent blood compatibility, suggesting a promising drug and gene co-delivery carrier in combined therapy to tumors.

Redox-responsive chemosensitive polyspermine delivers ursolic acid targeting to human breast tumor cells: The depletion of intracellular GSH contents arouses chemosensitizing effects.

Antitumor efficacy of ursolic acid (UA) is seriously limited due to its low hydrophilicity and needy bioavailability. To overcome these obstacles, chemosensitive polyspermine (CPSP) conjugated with UA and folic acid (FA) as a novel targeted prodrug was designed and successfully synthesized in this investigation. This prodrug not only showed high aqueous solubility, GSH-triggered degradation and good biocompatibility, but also exhibited better inhibition effect on the tumor cells proliferation in comparison with free UA. FA-CPSP-UA could down-regulate the generation of GSH and manifest excellent ability in enhancing antitumor efficacy. In addition, FA-CPSP-UA could inhibit the expression of MMP-9, which led to restricting MCF-7 cells migration. Taken together, the results indicated that FA-CPSP-UA, as a carrier, can efficiently deliver UA to folate receptor positive cancer cells and improve tumor therapy of UA by Chemosensitive effect.

Reduction-Responsive Codelivery System Based on a Metal-Organic Framework for Eliciting Potent Cellular Immune Response.

Utilizing nanoparticles to deliver subunit vaccines can be viewed as a promising strategy for enhancing the immune response, especially with regard to cellular immunity to fight against infectious viruses and malignant cancer. Nevertheless, its applications are still far from practicality because of some limitations such as high cost, non-biocompatibility, non-biodegradability, and the inefficient stimulation of cytotoxic T lymphocyte (CTL) response. In this study, we use metal-organic framework (MOF) MIL-101-Fe-NH2 nanoparticles as carriers to fabricate an innovative reduction-responsive antigen delivery system for cotransporting the antigen model ovalbumin (OVA) and an immune adjuvant, unmethylated cytosine-phosphate-guanine (CpG) oligonucleotide. In vitro cellular tests show that the MOF nanoparticles can not only greatly improve the uptake of OVA by the antigen-presenting cells but also smartly deliver both OVA and CpG into the same cell. By feat of the reductively controllable release of OVA and the promoting function of CpG, the delivery system can elicit strong cellular immunity and CTL response in mice. Moreover, the increased frequencies of effector memory T cells inspired by the delivery system indicate that it can induce a potent immune memory response. These results demonstrate that MOF nanoparticles are excellent vehicles for codelivering antigen and immune adjuvant and may find wider applications in biomedical fields.

Three-dimensional printing of shape memory hydrogels with internal structure for drug delivery.

Hydrogels with shape memory behavior and internal structure have wide applications in fields ranging from tissue engineering and medical instruments to drug delivery; however, creating the hydrogels has proven to be extremely challenging. This study presents a three-dimensional (3D) printing technology to fabricate the shape memory hydrogels with internal structure (SMHs) by combining sodium alginate (alginate) and pluronic F127 diacrylate macromer (F127DA). SMHs were constituted by a dual network structure. One is a stable network which is formed by F127DA photo-crosslinking; the other one is a reversible network which is formed by Ca2+ cross-linked alginate. SMHs recovery ratio was 98.15% in 10min after Ca2+ was removed in the Na2CO3 solution, and the elastic modulus remains essentially stable after the shape memory cycle. It showed that the drug releasing rate is more rapid compared with traditional drug-loaded hydrogels in in vitro experiments. The viability of 3T3 fibroblasts remained intact which revealed its excellent biocompatibility. Therefore, SMHs have a huge prospect for application in drug carriers and tissue engineering scaffold.

Melanoma mimicking Rosai-Dorfman disease.

Despite well-defined clinical and histopathological features of melanoma, atypical presentations mimicking other skin disorders can result in a delayed diagnosis or misdiagnosis and subsequent inappropriate treatment. Rosai-Dorfman disease (RDD) is a rare histiocytic disorder with unique clinical and histopathological features. We report a case of melanoma treated with cryotherapy that mimicked RDD both clinically and histopathologically. We compare this RDD-like melanoma to classic RDD, outlining the importance of clinicopathological correlation prior to treatment, as well as the potential pitfalls in diagnosis after cryotherapy of pigmented lesions.

Added Value of Computer-aided CT Image Features for Early Lung Cancer Diagnosis with Small Pulmonary Nodules: A Matched Case-Control Study.

Purpose To test whether computer-aided diagnosis (CAD) approaches can increase the positive predictive value (PPV) and reduce the false-positive rate in lung cancer screening for small nodules compared with human reading by thoracic radiologists. Materials and Methods A matched case-control sample of low-dose computed tomography (CT) studies in 186 participants with 4-20-mm noncalcified lung nodules who underwent biopsy in the National Lung Screening Trial (NLST) was selected. Variables used for matching were age, sex, smoking status, chronic obstructive pulmonary disease status, body mass index, study year of the positive screening test, and screening results. Studies before lung biopsy were randomly split into a training set (70 cancers plus 70 benign controls) and a validation set (20 cancers plus 26 benign controls). Image features from within and outside dominant nodules were extracted. A CAD algorithm developed from the training set and a random forest classifier were applied to the validation set to predict biopsy outcomes. Receiver operating characteristic analysis was used to compare the prediction accuracy of CAD with the NLST investigator's diagnosis and readings from three experienced and board-certified thoracic radiologists who used contemporary clinical practice guidelines. Results In the validation cohort, the area under the receiver operating characteristic curve for CAD was 0.9154. By default, the sensitivity, specificity, and PPV of the NLST investigators were 1.00, 0.00, and 0.43, respectively. The sensitivity, specificity, PPV, and negative predictive value of CAD and the three radiologists' combined reading were 0.95, 0.88, 0.86, and 0.96 and 0.70, 0.69, 0.64, and 0.75, respectively. Conclusion CAD could increase PPV and reduce the false-positive rate in the early diagnosis of lung cancer. © RSNA, 2017 Online supplemental material is available for this article.

Synthesis of Janus Au nanorods/polydivinylbenzene hybrid nanoparticles for chemo-photothermal therapy.

Chemo-photothermal therapy has attracted tremendous attention due to its synergistic effect in killing cancer cells, making it one of the most efficient therapies. Although most of the applied core-shell hybrid nanoparticles (NPs) can perform such a function, the lowering of their thermal efficiency through polymer coating and limited drug loading capacity severely limit their performance. Janus NPs with exposed metal and a polymer/silica matrix show improved chemo- and photothermal-efficiency, but have a complicated synthesis, and their loading capacity for hydrophobic drugs still needs to be optimized. Herein, we report the facile synthesis of Janus NPs comprising Au nanorods (NRs) and a hydrophobic polydivinylbenzene (PDVB) matrix. The UV-vis extinction of the Janus NPs is in the near infrared region (the region used in medicine), which makes it an ideal candidate for photothermal therapy, and the hydrophobic PDVB component is a good anticancer drug (curcumin) carrier for chemotherapy. With this combination of chemo- and photothermal-effects, a significant decrease in cell viability, migration, and invasion was realised, making the material a promising biomedical candidate for the treatment of cancer.

Clinical Virtual Reality: Emerging Opportunities for Psychiatry.

Virtual reality (VR) technology offers new opportunities for the development of innovative clinical research, assessment, and intervention tools. VR-based testing, training, teaching, and treatment approaches that would be difficult, if not impossible, to deliver with traditional methods are now being developed that take advantage of the assets that are available with VR technology. As research evidence continues to indicate clinical efficacy, VR applications are being increasingly regarded as providing innovative options for targeting the cognitive, psychological, motor, and functional impairments that result from various clinical health conditions. VR allows for the precise presentation and control of stimuli in dynamic, multisensory, 3D computer-generated simulations as well as providing advanced methods for capturing and quantifying behavioral responses. These characteristics support the rationale for the use of VR applications in clinical assessment, intervention, and training. This article begins with a brief review of the history of and rationale for the use of VR with clinical populations. It then details one use case for the clinical application of VR-the exposure-therapy treatment of anxiety disorders and posttraumatic stress disorder. Although significant work is cited in other areas of clinical VR (e.g., pain management, cognitive and physical assessment and rehabilitation, eating disorders, social skills, and clinical training), a full overview of such a broad literature is beyond the scope of this article. Thus, the authors have opted to provide more in-depth analysis of one specific clinical area that clearly illustrates how VR has been successfully applied and is supported by an encouraging and evolving scientific literature.

Aortic Arch Pathology: Surgical Options for the Aortic Arch Replacement.

Aortic arch surgery remains one of the most technically challenging procedures in cardiac surgery. It demands consideration of myocardial, brain, spinal cord, and lower body protection and rigorous surgical technique. Novel surgical approaches and refinements in brain and end organ protection strategies, liberal use of antegrade cerebral perfusion and moderate hypothermia have made arch repair safer. As endovascular technology and open surgical techniques evolve, aortic surgeons will need to continue to learn and incorporate these methods into practice in order to improve outcomes.

Neuroprotection Strategies in Aortic Surgery.

Neurologic injury is a potentially devastating complication of aortic surgery. The methods used in aortic surgery, including systemic cooling, initiation of circulatory arrest, and rewarming during the replacement of the aortic arch, are the most complex circulatory management and surgical procedures performed in modern-day surgery. Despite the plethora of published literature, neuroprotection in aortic surgery is largely based on observational studies and institutional-based practices. This article summarizes the current evidence and emerging strategies for neuroprotection in aortic arch operations.

High-resolution study of the 3D collagen fibrillary matrix of Achilles tendons without tissue labelling and dehydrating.

Knowledge of the collagen structure of an Achilles tendon is critical to comprehend the physiology, biomechanics, homeostasis and remodelling of the tissue. Despite intensive studies, there are still uncertainties regarding the microstructure. The majority of studies have examined the longitudinally arranged collagen fibrils as they are primarily attributed to the principal tensile strength of the tendon. Few studies have considered the structural integrity of the entire three-dimensional (3D) collagen meshwork, and how the longitudinal collagen fibrils are integrated as a strong unit in a 3D domain to provide the tendons with the essential tensile properties. Using second harmonic generation imaging, a 3D imaging technique was developed and used to study the 3D collagen matrix in the midportion of Achilles tendons without tissue labelling and dehydration. Therefore, the 3D collagen structure is presented in a condition closely representative of the in vivo status. Atomic force microscopy studies have confirmed that second harmonic generation reveals the internal collagen matrix of tendons in 3D at a fibril level. Achilles tendons primarily contain longitudinal collagen fibrils that braid spatially into a dense rope-like collagen meshwork and are encapsulated or wound tightly by the oblique collagen fibrils emanating from the epitenon region. The arrangement of the collagen fibrils provides the longitudinal fibrils with essential structural integrity and endows the tendon with the unique mechanical function for withstanding tensile stresses. A novel 3D microscopic method has been developed to examine the 3D collagen microstructure of tendons without tissue dehydrating and labelling. The study also provides new knowledge about the collagen microstructure in an Achilles tendon, which enables understanding of the function of the tissue. The knowledge may be important for applying surgical and tissue engineering techniques to tendon reconstruction.